DESCRIPTION (applicant's abstract): Dysregulation of the system has been associated with psychiatric disorders such as depression. CRF is thought to function as a central mediator of integrated autonomic, neuroendocrine, and behavioral responses to stress. The behavioral effects of CRF often resemble conditions of mild stress or arousal; norepinephrine (NE) has been proposed to regulate arousal and vigilance by enhancing the salience of sensory inputs to neurons. Thus, CRF and NE could interact to modulate the fundamental behavioral profile that an organism exhibits in response to its changing environmental conditions. The shell subregion of the nucleus accumbens (AcbSh) contains dense concentrations of CRF and NE, and is thought to integrate information processed in cortical, limbic, autonomic, and motor areas; AcbSh is thereby very well positioned to regulate the basic behavioral profile of an organism in response to its dynamic external milieu. AcbSh could thus be an important site in which CRF and NE systems act and possibly interact in the regulation of an organism's fundamental behavioral repertoire. The present proposal seeks to examine the behavioral roles of CRF and NE in the AcbSh, and the neurochemical and anatomical substrates of possible interactions between these systems within this region. This work may provide an important first step in characterizing the basic mechanisms through which an organism maintains behavioral homeostasis; understanding of these substrates might ultimately shed insight into some of the processes that become dysregulated in illnesses such as depression and anxiety disorders that are characterized by the expression of inappropriate behavioral responses to environmental contingencies.